The continuing controversy regarding the efficacy of, and optimal individualized approaches to, screening for the early detection of breast cancer, including the argument that conventional / traditional screening approaches may result in the detection of many cancers that are not likely to ultimately impact survival, stresses the importance of investigating alternative approaches to screening, in particular as related to younger women and / or women with denser than average age adjusted breast tissue who are at an elevated risk for developing breast cancer and in whom conventional mammography is known to be quite limited. Recent initiatives in many states require notifying women of their breast density. Women recommended for additional imaging (i.e., density BIRADS 3 and 4) constitutes between 40 and 50 percent of the screened population. The two possible high volume procedures being considered for this purpose are Whole Breast Ultrasound (WBUS) performed either manually or automatically and Digital Breast Tomosynthesis (DBT) that is being incorporated in routine clinical practice. Both DBT and WBUS technologies have advantages and limitations. To date, significant questions remain regarding the role that either may ultimately play in screening based breast imaging. As important, questions remain as to the marginal value of supplementary WBUS in a DBT based practice when DBT rather than FFDM is used as the baseline procedure. Therefore, at this time, it is important to validate / confirm te demonstrated potential for an acceptable performance for each of these modalities, as well as a significant performance improvement when using these approaches jointly and compare these performance levels, not only in terms of cancer detection and recall rates, but also in terms of the types of cancers likely to be detected by each imaging modality. As important, we will also assess experimentally the marginal value of WBUS as a supplementary imaging procedure to DBT based screening. The purpose of this project is to address these very issues by performing a prospective study on women who are most likely to benefit from the use of either WBUS and/or DBT or both in the screening environment. We propose to assess these questions in a sequentially selected population of consenting women participating in our screening program, which will include four of our 12 busiest sites encompassing both private and academic clinics and will involve 12 of our better performing 28 breast imaging radiologists with a wide range of experience levels and practice parameters. This project has broad and potentially significant implications on breast imaging as a whole. We have been collaborating as an integrated team in all scientific, operational, and clinical aspects of breast imaging, including, but not limited to, DBT and WBUS. The proposed project represents a natural, timely and warranted continuation and expansion of our ongoing investigations in this extremely important area of imaging based screening for the early detection of breast cancer, particularly those cancers that are unlikely to represent over-diagnosis.